Project Summary/Abstract Basic science and clinical research has shown that traumatic brain injury (TBI) results in immediate and transient increases in glucose uptake (CMRglc) to re-establish ionic equilibrium and neurochemical imbalances. This is rapidly followed by a prolonged period of glucose metabolic depression, a hallmark of TBI and a critical component of the cerebral metabolic crisis. During this depression the brain is vulnerable and there are many problems with glucose metabolism. We have shown that early administration of alternative substrates after injury reduces cell loss, improves cellular energy and early beahvioral outcomes. This grant will directly compare the capacity of alternative substrates to decrease metabolic crisis, improve mitochondrial energy, decrease free radical damage and improve long-term function in both male and female subjects. Findings from these studies will establish which brain fuels are optimal for recovery in both genders after TBI.